Metformin and lifestyle changes, either alone or in combination, counteracted the weight gain caused by atypical antipsychotic medications after an initial episode of schizophrenia, according to the findings of a prospective study.
These approaches also decrease waist circumference, body mass index, fasting glucose levels, insulin levels, and insulin resistance index in schizophrenia patients taking the drugs, compared with placebo, Dr. Ren-Rong Wu and associates at Central South University, Changsha, China, reported.
In what they described as the first double-blind placebo-controlled study to directly compare metformin and lifestyle interventions in a population of first-episode schizophrenia patients, the investigators randomly assigned 32 patients each to receive either 750 mg metformin alone daily, a placebo tablet alone, lifestyle interventions plus metformin, or lifestyle interventions plus placebo tablet, for 12 weeks.
All of the study subjects had developed their first episode of schizophrenia during the preceding year and had gained more than 10% of their predrug body weight during therapy with clozapine (Clozaril), olanzapine (Zyprexa), risperidone (Risperdal), or sulpiride. Most had been of normal weight before beginning treatment, and most were young adults.
All the subjects were living in the care of their parents or caregivers, who assisted with adherence to the interventions.
The lifestyle interventions included counseling; prescription of what the American Heart Association formerly called the step 2 diet—now known as the Therapeutic Lifestyle Changes diet—which allowed less than 30% of total calories from fat but did not decrease total daily caloric intake; and exercise such as walking, jogging, bicycling, sports, and vigorous activity such as chopping wood.
The subjects' weight decreased by 7.3% with metformin plus lifestyle interventions, by 4.9% with metformin alone, and by 2% with lifestyle interventions plus placebo. In contrast, weight continued to rise by 4.8% with placebo alone.
Similarly, all three treatment approaches significantly reduced mean fasting glucose, insulin levels, and insulin resistance index, while these measures significantly increased with placebo.
No major adverse events were attributed to the interventions. Ten of the subjects failed to complete the study, five of whom required hospitalization for exacerbation of psychosis.
For patients with schizophrenia who are taking atypical antipsychotic medications, “we recommend that lifestyle intervention[s] plus metformin be considered first for those with weight gain. If patients cannot tolerate or adhere poorly to lifestyle intervention[s], they should consider metformin alone,” Dr. Wu and associates said (JAMA 2008;299:185–93).
The authors noted that their study results may not be generalizable to Western populations, to people with schizophrenia who live independently, or to patients who have long-standing schizophrenia or who are older or more obese than these study subjects were when they began treatment.
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